β-Catenin Directs Long-Chain Fatty Acid Catabolism in the Osteoblasts of Male Mice

Endocrinology
Julie L FreyRyan C Riddle

Abstract

Wnt-initiated signaling through a frizzled receptor and the low-density lipoprotein-related receptor-5 coreceptor instructs key anabolic events during skeletal development, homeostasis, and repair. Recent studies indicate that Wnt signaling also regulates the intermediary metabolism of osteoblastic cells, inducing glucose consumption in osteoprogenitors and fatty acid utilization in mature osteoblasts. In this study, we examined the role of the canonical Wnt-signaling target, β-catenin, in the control of osteoblast metabolism. In vitro, Wnt ligands and agonists that stimulated β-catenin activation in osteoblasts enhanced fatty acid catabolism, whereas genetic ablation of β-catenin dramatically reduced oleate oxidation concomitant with reduced osteoblast maturation and increased glycolytic metabolism. Temporal ablation of β-catenin expression in osteoblasts in vivo produced the expected low-bone-mass phenotype and also led to an increase in white adipose tissue mass, dyslipidemia, and impaired insulin sensitivity. Because the expression levels of enzymatic mediators of fatty acid β-oxidation are reduced in the skeleton of β-catenin mutants, these results further confirm the role of the osteoblast in lipid metabolism and indicate...Continue Reading

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Citations

Aug 30, 2019·Nature Reviews. Endocrinology·Naomi DirckxRyan C Riddle
Oct 19, 2019·Cell Communication and Signaling : CCS·Yi-Heng HaoMaralice Conacci-Sorrell
Aug 17, 2018·Endocrinology and Metabolism·Megan C Moorer, Ryan C Riddle
Oct 20, 2020·Frontiers in Endocrinology·Nathalie S AlekosRyan C Riddle
Jan 5, 2021·The Journal of Clinical Investigation·Nivea Dias AmoedoRodrigue Rossignol
Jul 20, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Greig CouasnayFlorent Elefteriou

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